Proton pump inhibitors and histamine-2-receptor antagonists and pancreatic cancer risk: a nested case-control study

Background: The relationship between use of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H₂RAs) and pancreatic cancer risk has yet to be examined. Data from a range of studies suggest biologically plausible mechanisms, whereby these drugs (or the conditions for which they are prescribed) may affect pancreatic cancer risk. The objective of this study was to investigate the relationship between use of PPIs/H₂RAs and pancreatic cancer risk.

Methods: A nested case – control study was conducted within the UK general practice research database (GPRD). Cases had a diagnosis of exocrine pancreatic cancer and controls were matched to cases on general practice site, sex and year of birth. Exposure to PPIs and to H₂RAs since entry into GPRD until 2 years before the diagnosis date (corresponding date in controls) and in the 5 years before the diagnosis date were separately assessed. Conditional logistic regression analyses were used to generate odds ratios (ORs) and 95% confidence intervals (CIs) associated with PPI or H₂RA use compared with nonuse.

Results: Ever use of PPIs since entry into the GPRD (excluding the 2 years prior to diagnosis) was not associated with risk of pancreatic cancer; OR (95% CI) 1.02 (0.85 – 1.22). Neither the dose nor the duration of PPI or H₂RA use was associated with pancreatic cancer risk. No consistent patterns of association were seen when cumulative exposure (dose and duration) to these drugs was examined separately or together.

Conclusion: PPI/H₂RA use, in a UK population, was not associated with pancreatic cancer risk.

The role of operations management in public sector policy and practice alignment: a local government analysis

In responding to the demand for change and improvement, local government has applied a plethora of operations management-based methods, tools and techniques. This article explores how these methods, specifically in the form of performance management models, are used to improve alignment between central government policy and local government practice, an area which has thus far been neglected in the literature. Using multiple case studies from Environmental Waste Management Services, this research reports that models derived in the private sector are often directly ‘implanted’ into the public sector. This has challenged the efficacy of all performance management models. However, those organisations which used models most effectively did so by embedding (contextualisation) and extending (reconceptualisation) them beyond their original scope. Moreover, success with these models created a cumulative effect whereby other operations management approaches were probed, adapted and used.

CASTING SOLVENT CONTROLLED-RELEASE OF CHLORHEXIDINE FROM ETHYLCELLULOSE FILMS PREPARED BY SOLVENT EVAPORATION

Chlorhexidine release from ethylcellulose films east from solvents of different dichloromethane/ethanol compositions was studied. Release rate was proportional to the square root of time. Increased ethanol content within the casting solvent significantly enhanced release rate. Release rate and cumulative mass released at different time periods (5, 10, 15 and 25 days) were proportional to the solubility parameter of the casting solvent.

Marine reserve designation, trophic cascades and altered community dynamics

Marine ecosystems and their associated populations are increasingly at risk from the cumulative impacts of many anthropogenic threats that increase the likelihood of species extinction and altered community dynamics. In response, marine reserves can be used to protect exploited species and conserve biodiversity. The increased abundance of predatory species in marine reserves may cause indirect effects along chains of multi-trophic interactions. These trophic cascades can arise through direct predation, density-mediated indirect interactions (DMIIs), or indirect behavioural effects, termed trait-mediated indirect interactions (TMIIs). The extent of algal cover and the abundance of 4 primary consumers were determined in Lough Hyne, which was designated Europe's first marine nature reserve in 1981. The primary consumers were the sea urchin Paracentrotus lividus, the topshell Gibbula cineraria, the oyster Anomia ephippium, and the scallop Chlamys varia. The abundances of 3 starfish species (Marthasterias glacialis, Asterias rubens, and Asterina gibbosa) were also determined, as were 2 potential crustacean predators, Necora puber and Carcinus maenas. These data were compared with historical data from a 1962 (prey) and a 1963 (predator) survey to determine the nature of community interactions over adjacent trophic levels. The present study reveals a breakdown in population structure of the 4 surveyed prey species. Marine reserve designation has led to an increase in predatory crabs and M. glacialis, a subsequent decrease in primary consumers, especially the herbivore P. lividus, and an increase in macroalgal cover which is indicative of a trophic cascade. The study shows that establishing a Marine Reserve does not guarantee that conservation benefits will be distributed equally.

Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials

Background Moderate di?erences in e?cacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could a? ect treatment choices. We sought any such di?erences.

Methods We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plusanthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44 000); one anthracyclinebased regimen versus another (n=7000) or versus cyclo phosphamide, methotrexate, and ?uorouracil (CMF; n=18 000); and polychemotherapy versus no chemotherapy (n=32 000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to de? ne standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported.

Findings In trials adding four separate cycles of a taxane to a ?xed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided signi?cance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no signi?cant di?erence (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or
standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little a? ected by age, nodal status, tumour diameter or di?erentiation (moderate or poor; few were well di?erentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality di?erences paralleled breast cancer mortality di?erences, despite taxane, anthracycline, and other toxicities.

Interpretation 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute bene?t, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both.

Mechanical fatigue and spectrum analysis of small-satellite

Mechanical fatigue due to environmental loads and spectrum analysis due to launch loads of the primary structure of a low cost, low-earth orbit small satellite intended for earth observation missions are presented. The payload of the satellite under consideration is a precise optical unit to image the earth’s surface having a mass of 45 kg. 3-D Finite Element Model for the satellite structure is generated by applying substructure method. Modal analysis is required to determine natural frequencies of the satellite and define its mode shape. Then, ranking of mode shapes according to specific constraint is performed. Harmonic analysis at resonance frequencies with the highest ranking is done and cumulative fatigue damage analysis is performed. Spectrum analysis is performed for Small Sat structure to verify the satellite structure reliability under all dynamic random vibration loads applied during transportation and launch cases.

Carotenoids and co-antioxidants in age-related maculopathy:design and methods

Age-related macular degeneration (AMD), is the leading cause of blind registration in the Western World among individuals 65 years or older. Early AMD, a clinical state without overt functional loss, is said to be present clinically when yellowish deposits known as drusen and/or alterations of fundus pigmentation are seen in the macular retina. Although the etiopathogenesis of AMD remains uncertain, there is a growing body of evidence in support of the view that cumulative oxidative damage plays a causal role. Appropriate dietary antioxidant supplementation is likely to be beneficial in maintaining visual function in patients with AMD, and preventing or delaying the progression of early AMD to late AMD. The Carotenoids in Age-Related Maculopathy (CARMA) Study is a randomized and double-masked clinical trial of antioxidant supplementation versus placebo in 433 participants with either early AMD features of sufficient severity in at least one eye or any level of AMD in one eye with late AMD (neovascular AMD or central geographic atrophy) in the fellow eye. The aim of the CARMA Study is to investigate whether lutein and zeaxanthin, in combination with co-antioxidants (vitamin C, E, and zinc), has a beneficial effect on visual function and/or prevention of progression from early to late stages of disease. The primary outcome is improved or preserved distance visual acuity at 12 months. Secondary outcomes include improved or preserved interferometric acuity, contrast sensitivity, shape discrimination ability, and change in AMD severity as monitored by fundus photography. This article outlines the CARMA Study design and methodology, including its rationale.

On the Qualitative Comparison of Decisions Having Positive and Negative Features

Making a decision is often a matter of listing and comparing positive and negative arguments. In such cases, the evaluation scale for decisions should be considered bipolar, that is, negative and positive values should be explicitly distinguished. That is what is done, for example, in Cumulative Prospect Theory. However, contrary to the latter framework that presupposes genuine numerical assessments, human agents often decide on the basis of an ordinal ranking of the pros and the cons, and by focusing on the most salient arguments. In other terms, the decision process is qualitative as well as bipolar. In this article, based on a bipolar extension of possibility theory, we define and axiomatically characterize several decision rules tailored for the joint handling of positive and negative arguments in an ordinal setting. The simplest rules can be viewed as extensions of the maximin and maximax criteria to the bipolar case, and consequently suffer from poor decisive power. More decisive rules that refine the former are also proposed. These refinements agree both with principles of efficiency and with the spirit of order-of-magnitude reasoning, that prevails in qualitative decision theory. The most refined decision rule uses leximin rankings of the pros and the cons, and the ideas of counting arguments of equal strength and cancelling pros by cons. It is shown to come down to a special case of Cumulative Prospect Theory, and to subsume the “Take the Best” heuristic studied by cognitive psychologists.

Breast Cancer Risk in Relation to Occupations with Exposure to Carcinogens and Endocrine Disruptors:a Canadian Case-Control Study

Background

Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours.

Methods

1005 breast cancer cases referred by a regional cancer center and 1147 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case?control design, exposure effects were estimated using conditional logistic regression.

Results

Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5).

Conclusions

These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and demonstrate the value of detailed work histories in environmental and occupational epidemiology.

Laser-engineered dissolving microneedles for active transdermal delivery of nadroparin calcium

There is an urgent need to replace the injection currently used for low molecular weight heparin (LMWH) multidose therapy with a non- or minimally invasive delivery approach. In this study, laser-engineered dissolving microneedle (DMN) arrays fabricated from aqueous blends of 15% w/w poly(methylvinylether-co-maleic anhydride) were used for the first time in active transdermal delivery of the LMWH nadroparin calcium (NC). Importantly, an array loading of 630 IU of NC was achieved without compromising the array mechanical strength or drug bioactivity. Application of NC-DMNs to dermatomed human skin (DHS) using the single-step 'poke and release' approach allowed permeation of approximately 10.6% of the total NC load over a 48-h study period. The cumulative amount of NC that permeated DHS at 24 h and 48 h attained 12.28 ± 4.23 IU/cm and 164.84 ± 8.47 IU/cm , respectively. Skin permeation of NC could be modulated by controlling the DMN array variables, such as MN length and array density as well as application force to meet various clinical requirements including adjustment for body mass and renal function. NC-loaded DMN offers great potential as a relatively low-cost functional delivery system for enhanced transdermal delivery of LMWH and other macromolecules. © 2012 Elsevier B.V. All rights reserved.

Systematically Identifying Relevant Research : Case Study on Child Protection Social workers' Resilience

Context: The development of a consolidated knowledge base for social work requires rigorous approaches to identifying relevant research. Method: The quality of 10 databases and a web search engine were appraised by systematically searching for research articles on resilience and burnout in child protection social workers. Results: Applied Social Sciences Index and Abstracts, Social Services Abstracts and Social Sciences Citation Index (SSCI) had greatest sensitivity, each retrieving more than double than any other database. PsycINFO and Cumulative Index to Nursing and Allied Health (CINAHL) had highest precision. Google Scholar had modest sensitivity and good precision in relation to the first 100 items. SSCI, Google Scholar, Medline, and CINAHL retrieved the highest number of hits not retrieved by any other database. Conclusion: A range of databases is required for even modestly comprehensive searching. Advanced database searching methods are being developed but the profession requires greater standardization of terminology to assist in information retrieval.

Moving in and out of poverty - The impact of welfare regimes on poverty dynamics in the EU

Although many of the debates around social exclusion and cumulative disadvantage relate to processes that occur across time, there has been relatively little research into poverty dynamics except in a few notable countries such as Britain, the USA and Germany. This neglect is almost entirely because of the absence of comparative longitudinal data on income for other countries, but it is regrettable given the central importance of this area. By studying poverty dynamics we not only get a better insight into the processes leading to patterns of disadvantage and inequality, but we can also understand better the influence of different welfare state regimes on the social risks experienced by different types of individuals and households. The extent to which different national contexts protect their citizens from poverty persistence, or vary in the factors leading to poverty persistence, tells us a great deal about the workings of their socioeconomic systems and welfare regimes.

In this article we use the recent availability of five waves of the European Community Household Panel Survey to outline the nature of poverty persistence and poverty dynamics across a large number of countries. In doing so we ask three important questions. First, is poverty a more common experience when viewed longitudinally rather than cross-sectionally, and how is this affected by the income poverty line used? Second, can we identify a tendency toward poverty persistence, and does this vary in its extent across countries? Third and lastly, what types of events are more likely to lead to entry into and exit from poverty, and does the importance of these events differ between countries? The article shows that the experience of poverty is far wider than is appreciated from cross-sectional data, and also tends to be more concentrated on a particular population than would be expected from cross-sectional rates. Moreover, the pattern of poverty persistence is congruent with welfare regime theory. The importance of country institutions and welfare regimes is also underlined by the finding that social welfare and market incomes play different roles in poverty transitions across countries, and that Southern European, or residualist, welfare regimes focus poverty risks on the experience of the household's primary earner to a far greater extent than Northern European welfare states do.

Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays

A plethora of studies have described the in vitro assessment of dissolving microneedle (MN) arrays for enhanced transdermal drug delivery, utilising a wide variety of model membranes as a representation of the skin barrier. However, to date, no discussion has taken place with regard to the choice of model skin membrane and the impact this may have on the evaluation of MN performance. In this study, we have, for the first time, critically assessed the most common types of in vitro skin permeation models - a synthetic hydrophobic membrane (Silescol(®) of 75 µm) and neonatal porcine skin of definable thickness (300-350 µm and 700-750 µm) - for evaluating the performance of drug loaded dissolving poly (methyl vinyl ether co maleic acid) (PMVE/MA) MN arrays. It was found that the choice of in vitro skin model had a significant effect on the permeation of a wide range of small hydrophilic molecules released from dissolving MNs. For example, when Silescol(®) was used as the model membrane, the cumulative percentage permeation of methylene blue 24h after the application of dissolvable MNs was found to be only approximately 3.7% of the total methylene blue loaded into the MN device. In comparison, when dermatomed and full thickness neonatal porcine skin were used as a skin model, approximately 67.4% and 47.5% of methylene blue loaded into the MN device was delivered across the skin 24h after the application of MN arrays, respectively. The application of methylene blue loaded MN arrays in a rat model in vivo revealed that the extent of MN-mediated percutaneous delivery achieved was most similar to that predicted from the in vitro investigations employing dermatomed neonatal porcine skin (300-350 µm) as the model skin membrane. On the basis of these results, a wider discussion within the MN community will be necessary to standardise the experimental protocols used for the evaluation and comparison of MN devices.

Hair cortisol reflects socio-economic factors and hair zinc in preschoolers

This study examined the relationship between children's hair cortisol and socioeconomic status of the family, as measured by parental education and income. Low family socioeconomic status has traditionally been considered a long-term environmental stressor. Measurement of hair cortisol provides an integrated index of cumulative stress exposure across an extended period of time. The present study is the first to examine the relationship between hair cortisol and parental education as well as parental income in a representative sample of preschoolers. Data on hair cortisol, family income, and parental education were collected for a representative sample of 339 children (Mean age=4.6 years; SD=.5 years) from across 23 neighbourhoods of the city of Vancouver, Canada. As maternal education was shown previously to be associated with hair zinc level, hair zinc measurements were included as well in order to explore potential relationships between hair zinc and hair cortisol. The relationship between hair cortisol and parental education was examined using hierarchical regression, with hair zinc, gender, age, and single parenthood included as covariates. Maternal and paternal education both were correlated significantly with hair cortisol (r=-0.18; p=.001). The relationship remained statistically significant even after controlling for all demographic covariates as well as for hair zinc and after taking the neighbourhood-level clustering of the data into account. Parental income, on the other hand, was not related significantly to children's hair cortisol. This study provides evidence that lower maternal and paternal education are associated with higher hair cortisol levels. As hair cortisol provides an integrated index of cortisol exposure over an extended time period, these findings suggest a possibly stable influence of SES on the function of the hypothalamic-pituitary-adrenal (HPA) axis. Cumulative exposure to cortisol during early childhood may be greater in children from low socio-economic backgrounds, possibly through increased exposure to environmental stressors.

Assessing pain in preterm infants in the neonatal intensive care unit:moving to a 'brain-oriented' approach

Preterm infants in the neonatal intensive care unit undergo repeated exposure to procedural and ongoing pain. Early and long-term changes in pain processing, stress-response systems and development may result from cumulative early pain exposure. So that appropriate treatment can be given, accurate assessment of pain is vital, but is also complex because these infants' responses may differ from those of full-term infants. A variety of uni- and multidimensional assessment tools are available; however, many have incomplete psychometric testing and may not incorporate developmentally important cues. Near-infrared spectroscopy and/or EEG techniques that measure neonatal pain responses at a cortical level offer new opportunities to validate neonatal pain assessment tools.